A compound represented by the formula (VI-a) (hereinafter referred to as compound (VI-a)):
wherein R1 represents a hydrogen atom, a substituted or unsubstituted alkyl, or an alkali metal; ora lactone form of compound (VI-a) represented by the formula (VI-b) (hereinafter referred to as compound (VI-b)):
is known to inhibit HMG-CoA reductase and exhibit an action of reducing serum cholesterol (The Journal of Antibiotics, 29, 1346 (1976)).
There have been several reports regarding methods for producing compound (VI-a) or compound (VI-b) from a compound represented by the formula (V-a) (hereinafter referred to as compound (V-a)):
wherein R1 has the same definition as the above; or from the lactone form of compound (V-a) represented by the formula (V-b) (hereinafter referred to as compound (V-b):
using a microorganism.
Specifically, Japanese Patent Application Laid-Open (kokai) No. 57-50894 describes a method which uses filamentous fungi; both Japanese Patent Application Laid-Open (kokai) No. 7-184670 and International Publication WO96/40863 describe a method which uses Actinomycetes; and Japanese Patent No. 2672551 describes a method which uses recombinant Actinomycetes. As is well known, however, since filamentous fungi and Actinomycetes grow with filamentaous form by elongating hyphae, the viscosity of the culture in a fermentor increases.
This often causes a shortage of oxygen in the culture, and since the culture becomes heterogeneous, reaction efficiency tends to be reduced. In order to resolve this oxygen shortage and maintain homogenousness of the culture, the agitation rate of the fermentor should be raised, but by raising the agitation rate, hyphae are sheared and, as a result, activity of the microorganisms tends to decrease (Basic Fermentation Engineering (Hakko Kogaku no Kiso) p. 169–190, P. E Stansbury, A. Whitaker, Japan Scientific Societies Press (1988)).